Without limiting the scope of the invention, its background is described in connection with controlled release vaccines and use of Brucella strains in vaccine manufacturing.
Andrews and Lowry have described compositions and methods for the diagnosis and prevention of B. abortus infection in U.S. Patent Application Publication No. 2011/0177127. The invention describes a method of detecting a Brucella abortus infection in an animal, comprising the steps of: a) obtaining a biological sample from said animal; and b) detecting the presence of at least one antibody immunologically specific for at least one Brucella abortus protein, wherein the presence of antibodies to the Brucella abortus protein indicates a Brucella abortus infection in said animal.
At present, no human brucellosis vaccine is available even though Brucella species are isolated from 86 countries, with 500,000 new cases of brucellosis appearing each year throughout Latin America, the Mediterranean littoral, Arabian peninsula, Africa, central Asia and the Far East (WHO, 2006); as a result, prevention of human brucellosis has focused upon the reduction in animal disease. The animal vaccine strains employed today are fortuitous isolates attenuated in ability to cause abortion due to reduced replication in reproductive tissues. The attenuation of these mutants does not extend to reticuloendothelial disease observed in mice and in humans, except in the case of the rough strain RB51. The lack of genetic definition of fortuitous isolates limits the usefulness of vaccine strains, preventing complete description of their stability, and warrants caution when applied to human use as disclosed in Sangari et al (1998) Vaccine 16, 1640-5 and Schurig et al (1991) Vet. Microbiol. 28, 171-88. Of the currently available vaccine strains, only B. abortus S19 and B. melitensis Rev 1 have been tested in humans as provided for in Spink et al. Bull World Health Organ (1962) 26, 409-19 and Spink & Thompson (1953) JAMA 153, 1162-1165, which are hereby incorporated by reference. Revl was found to be highly unsuitable with ⅔ of the “volunteers” exhibiting symptoms of disease and colonization by the organism. However, a subculture of S19 referred to as 19-BA provided results that are more palatable. Only two volunteers (12%) exhibited symptoms of disease, and the organism was isolated from one of these volunteers. 19-BA was originally used to vaccinate at least 3 million people in the Soviet Union as described in Vershilova Bull World Health Organ (1961) 24, 85-9. These investigators concluded that there were more problems due to hypersensitivity than to persistence of the organism. Eight percent complained of headache and malaise, and 2% showed signs of febrile illness. Clearly, a vaccine with this much side effect would not be and should not be tolerated given our current state of knowledge. Given the potential threat this organism poses, there is a need to develop a better human vaccine.
One such example of a live vaccine against brucellosis is described in U.S. Pat. No. 7,541,447 issued to Ugalde et al. (2009). The Ugalde invention comprises a live vaccine for immunization, prophylaxis or treatment of brucellosis comprising a bacterium modified by partial or complete deletion of the pgm gene, rendering the bacterium incapable of synthesizing a key enzyme in the metabolism of bacterial sugars. The vaccine of the '447 patent discloses nucleotide sequence fragments having the aforementioned deletion and is either lyophilized or is in a pharmaceutical vehicle.